The specialized functions of platelets are primarily involved in thrombosis and hemostasis. In performing these functions, the plasma membrane plays a central role. The membrane has receptors for the various stimuli which activate platelets, and it is the membrae surface which is altered such that platelets will aggregate. It is becoming increasingly apparent that an understanding of the platelet's role in thrombosis and hemostasis is dependent upon a molecular identification of the components involved in these reactions. In this application, we propose to investigate the molecular properties of some of these reactions. One is the thrombin receptor on the platelet surface. We have previously shown that glycoprotein V is specifically hydrolyzed during thrombin activation of platelets; recently, we have purified this glycoprotein to apparent homogeneity. The proposed experiments are designed to characterize the molecular properties of glycoprotein V and test our hypothesis that glycoprotein V is the thrombin receptor. Another series of experiments involves the polymerization of actin and its association with the inner aspect of the membrane. Our experiments are designed to characterize these reactions further and determine the role of the calcium-dependent protease in platelet cytoskeletal structure. A final series of experiments concerns the calcium dependency on membrane surface reactions. We have recently found that thrombin-sensitive protein (TSP) reversibly binds to the membrane surface of platelets and that binding is calcium-dependent. We propose to identify TSP receptors and determine if TSP has a function in platelet-specific reactions.